There is no universally accepted method to enhance the beneficial effects of rehabilitative treatment after stroke, the number-one cause of long-term disability among adults. Noninvasive stimulation of the human motor cortex enhances the beneficial effects of motor training on use-dependent plasticity in healthy humans, consistent with emerging information in the basic science domain and could influence functional recovery after stroke. Here, I propose to use Transcranial Direct Current Stimulation (tDCS), a mild, painless form of noninvasive cortical stimulation that is well tolerated, to test Hypothesis 1, that tOCS combined with standardized rehabilitative treatment (SRT) after stroke will elicit more prominent improvement in arm-hand motor function (primary endpoint measure: upper extremity component of the Fugl-Meyer test, uFM) than sham+SRT in a double blind, sham-controlled clinical trial. We predict that the tDCS-treated group will experience more prominent improvement in uFM than the sham- treated group. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (IMS) obtained before and after both interventions, will provide information on the neural substrates underlying the recovery process. We will test Hypothesis 2, that improved recovery in the tOCS-treated group will be associated with (a) increased fMRI activity in ipsilesional primary motor (M1) and dorsal premotor (PMd) cortices relative to the sham-treated group and (b) ipsilesional M1 and PMd contribute to functional improvement because a "virtual lesion" using TMS applied to M1 and PMd will transiently delay reaction time in the paretic hand, documenting a cause- effect link between the two. This is a phase 2 study with potential impact on how stroke patients are treated that will allow Dr. Hodics to acquire expertise in studying mechanisms of human neuroplasticity using tDCS, TMS and fMRI (Drs. Cohen's and Xu's expertise) in the setting of a double blind clinical trial in Neurorehabilitation (Dr. Dromerick's expertise). [unreadable] [unreadable] [unreadable]